Novel Leukocyte Modulator Device Reduces the Inflammatory Response to Cardiopulmonary Bypass

Abstract

Leukocyte activation during cardiopulmonary bypass (CPB) promotes a systemic inflammatory response that contributes to organ injury and postoperative organ dysfunction. A leukocyte modulatory device (L-MOD) for use during (and after) CPB to limit leukocyte-mediated organ injury was tested in a preclinical model. Twenty-two pigs underwent 180 minutes of CPB and 5 hours postoperative observation. Pigs received no intervention (group 1, n = 9), 3 hours of therapy by incorporation of L-MOD into the CPB circuit (group 2, n = 6), or 8 hours of therapy using a femoral venovenous L-MOD circuit during and after CPB (group 3, n = 7). Leukocyte activation was increased at the end of CPB and leukocyte counts, namely neutrophils, increased postoperatively in most animals. These indices trended much lower in group 3. Systemic vascular resistance was not as reduced post-CPB for the L-MOD-treated pigs, and urine output was significantly greater for group 3 (p < 0.01). At 5 hours post-CPB, group 3 had a lower troponin-I (1.59 ± 0.68 ng/ml) than group 1 or group 2 (3.97 ± 2.63 and 3.55 ± 2.04 ng/ml, respectively, p < 0.05) and a lower urine neutrophil gelatinase-associated lipocalin (7.57 ± 3.59 ng/ml) than the average of the other groups (50.71 ± 49.17, p < 0.05). These results demonstrate the therapeutic potential of L-MOD therapy to mitigate the inflammatory response to CPB. Eight hours of venovenous L-MOD resulted in less organ injury and post-op organ dysfunction in this model.

Extracorporeal Immunomodulation Treatment and Clinical Outcomes in ICU COVID-19 Patients

“…An inclusion criterion of intent to treat with SCD for at least 96 hours was included in the original clinical protocol due to prior clinical experience demonstrated that 72 to 96 hours of treatment was required to see clinical and laboratory improvement. For the CC group, all ICU patients from CRRTnet were identified with COVID-19 disease and selected after meeting all inclusion/exclusion criteria similar to the treated group ( 27 ). Only patients from the registry that began CRRT treatment during the study period were included into the CC group.…”

“…These bound leukocytes are deactivated and returned back to the systemic circulation (20). This continuous cell processing activity results in measurable diminution of excessive inflammatory responses with improvement of solid organ dysfunction in a variety of preclinical and clinical studies, including sepsis, AKI, ischemia/ reperfusion injury, intracerebral hemorrhage, cardiopulmonary bypass, chronic kidney disease, and type 2 diabetes mellitus (21)(22)(23)(24)(25)(26)(27)(28). This approach was recently evaluated under expanded/emergency use in four ICU COVID-19 patients with cytokine storm and severe ARDS requiring ECMO, and the encouraging results in the first two cases treated were reported (29).…”

Translation of Immunomodulatory Therapy to Treat Chronic Heart Failure: Preclinical Studies to First in Human

“…Accordingly, the extracorporeal immunomodulation approach with SCD treatment warranted an evaluation first in a preclinical model of systolic CHF prior to translation into the clinical setting. In preclinical models, SCD therapy has shown efficacy in acute multiorgan injury in severe sepsis, cardiopulmonary bypass, intracerebral hemorrhage (ICH), and ischemia/reperfusion injury (IRI) (10)(11)(12)(13)17). This device has been tested in 6 clinical studies in ICU patients with acute kidney injury and multiorgan dysfunction requiring dialysis and COVID-19 patients with adult respiratory distress syndrome (ARDS) with improved clinical outcomes and no device-related serious adverse events (14)(15)(16)18,19,23).…”

“…This continuous autologous cell processing activity results in measurable diminution of excessive inflammatory responses with improvement of solid organ dysfunction in a variety of preclinical and clinical studies, including sepsis, acute kidney injury, ischemia/reperfusion injury, intracerebral hemorrhage, cardiopulmonary bypass, adult respiratory distress syndrome, chronic kidney disease, and type 2 diabetes mellitus (10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”

Neutrophil Counts, Neutrophil-to-Lymphocyte Ratio, and Systemic Inflammatory Response Index (SIRI) Predict Mortality after Off-Pump Coronary Artery Bypass Surgery

“…The relationship between surgical intervention and cardiopulmonary bypass has been widely postulated [ 17 , 18 , 19 , 20 ]. Despite surgical challenges, the off-pump technique (off-pump coronary artery bypass surgery, OPCAB) can be performed safely by experienced surgeons and may rule out the risk of inflammatory activation that is secondary to CPB application [ 21 ].…”